Altered urinary tetrahydroisoquinoline derivatives in patients with Tourette syndrome: reflection of dopaminergic hyperactivity?

Capetian, Philipp; Roessner, Veit; Korte, Caroline; Walitza, Susanne; Riederer, Franz; Taurines, Regina; Gerlach, Manfred; Möser, Andreas

doi:10.1007/s00702-020-02289-6

Cited by 11 publications

(8 citation statements)

References 18 publications

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“…8 On the other hand, increased levels of isoquinoline derivatives present following alcohol consumption, such as SAL, 49 due to acetaldehyde production needed for their synthesis, are not associated with an increased risk of PD development. 50 What is more, higher urinary concentrations of SAL and NMSAL were found in Tourette syndrome and Tourette syndrome with ADHD patients (yet not de novo) 51 as well as in adolescents with ADHD only 52 compared with healthy controls. Thus, such increased levels of SAL and its derivatives might be a consequence of impaired dopaminergic pathways but not an underlying and direct cause of neurodegeneration.…”

Section: ■ Discussionmentioning

confidence: 99%

Neuroprotective Activity of Enantiomers of Salsolinol and N-Methyl-(R)-salsolinol: In Vitro and In Silico Studies

Kurnik-Łucka,

Latacz,

Bucki

et al. 2023

ACS Omega

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Salsolinol (1-methyl-1,2,3,4-tetrahydroisoquinoline-6,7-diol) is a close structural analogue of dopamine with an asymmetric center at the C1 position, and its presence in vivo, both in humans and rodents, has already been proven. Yet, given the fact that salsolinol colocalizes with dopamine-rich regions and was first detected in the urine of Parkinson’s disease patients, its direct role in the process of neurodegeneration has been proposed. Here, we report that R and S enantiomers of salsolinol, which we purified from commercially available racemic mixture by means of high-performance liquid chromatography, exhibited neuroprotective properties (at the concentration of 50 μM) toward the human dopaminergic SH-SY5Y neuroblastoma cell line. Furthermore, within the study, we observed no toxic effect of N-methyl-(R)-salsolinol on SH-SY5Y neuroblastoma cells up to the concentration of 750 μM, either. Additionally, our molecular docking analysis showed that enantiomers of salsolinol should exhibit a distinct ability to interact with dopamine D2 receptors. Thus, we postulate that our results highlight the need to acknowledge salsolinol as an active dopamine metabolite and to further explore the neuroregulatory role of enantiomers of salsolinol.

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Section: ■ Discussionmentioning

confidence: 99%

Neuroprotective Activity of Enantiomers of Salsolinol and N-Methyl-(R)-salsolinol: In Vitro and In Silico Studies

Kurnik-Łucka,

Latacz,

Bucki

et al. 2023

ACS Omega

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“…Norsalsolinol (NSAL) regulates the transmission and metabolism of DA in the CNS in vivo. A case–control study reported by Capetian P in 2021 showed that the urinary concentrations of NSAL were significantly increased in patients with TS, indicating that dopaminergic hyperactivity is involved in the pathophysiology of TS [ 15 ]. In a study assessing changes in DA in TS patients by positron emission tomography (PET), Steeves and colleagues showed that, after deep brain stimulation, the clinical improvement was related to decreased DA release and upregulation of DA receptors [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

A Pilot Study on Plasma and Urine Neurotransmitter Levels in Children with Tic Disorders

Qian

Tan²,

Sun

et al. 2022

Brain Sciences

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Background: Tic disorders (TDs), including Tourette syndrome, are childhood-onset neuropsychiatric disorders characterized by motor and/or vocal tics that commonly affect children’s physical and mental health. The pathogenesis of TDs may be related to abnormal neurotransmitters in the cortico-striatal-thalamo-cortical circuitry, especially dopaminergic, glutamatergic, and serotonergic neurotransmitters. The purpose of this study was to preliminarily investigate the differences in the three types of neurotransmitters in plasma and urine between children with TD and healthy children. Methods: We collected 94 samples of plasma and 69 samples of urine from 3–12-year-old Chinese Han children with TD before treatment. The plasma and urine of the same number of healthy Chinese Han children, matched for age and sex, participating in a physical examination, were collected. Ultra-performance liquid chromatography-tandem mass spectrometry was used to detect the three types of neurotransmitters in the above samples. Results: The plasma levels of norepinephrine, glutamic acid, and γ-aminobutyric acid, and the urine levels of normetanephrine and 5-hydroxyindoleacetic acid were higher in the TD children than in healthy children. The area under the curve (AUC) values of the above neurotransmitters in plasma and urine analyzed by receiver operating characteristic curve analysis were all higher than 0.6, with significant differences. Among them, the combined AUC of dopamine, norepinephrine, normetanephrine, glutamic acid, and γ-aminobutyric acid in the 8–12-year-old subgroup was 0.930, and the sensitivity and specificity for TD were 0.821 and 0.974, respectively (p = 0.000). Conclusions: There are differences in plasma and urine neurotransmitters between TD children and healthy children, which lays a foundation for further research on the pathogenesis of TD.

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“…The dopaminergic neurotransmission and its metabolism in the central nervous system of non-medicated patients with TD ( n = 7), TD + ADHD ( n = 12), and healthy controls ( n = 19) was recently investigated by Capetian et al [ 49 ]. They determined Tetrahydroisoquinolines (TIQs; modulating dopamine and thus giving another perspective on monoaminergic dysfunction [ 67 ]) in the urine by a two-phase chromatographic approach.…”

Section: Level “Abnormal Brain Conditions”mentioning

confidence: 99%

Co-Occurrence of Tic Disorders and Attention-Deficit/Hyperactivity Disorder—Does It Reflect a Common Neurobiological Background?

Rothenberger

Heinrich

2022

Biomedicines

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Background: The co-existence of tic disorders and attention-deficit/hyperactivity disorder (TD + ADHD) has proven to be highly important in daily clinical practice. The factor ADHD is not only associated with further comorbidities, but also has a long-term negative psychosocial effect, while the factor TD is usually less disturbing for the major part of the patients. It remains unclear how far this is related to a different neurobiological background of the associated disorders or whether TD + ADHD reflects a common one. Objective: This review provides an update on the neurobiological background of TD + ADHD in order to better understand and treat this clinical problem, while clarifying whether an additive model of TD + ADHD holds true and should be used as a basis for further clinical recommendations. Method: A comprehensive research of the literature was conducted and analyzed, including existing clinical guidelines for both TD and ADHD. Besides genetical and environmental risk factors, brain structure and functions, neurophysiological processes and neurotransmitter systems were reviewed. Results: Only a limited number of empirical studies on the neurobiological background of TD and ADHD have taken the peculiarity of co-existing TD + ADHD into consideration, and even less studies have used a 2 × 2 factorial design in order to disentangle the impact/effects of the factors of TD versus those of ADHD. Nevertheless, the assumption that TD + ADHD can best be seen as an additive model at all levels of investigation was strengthened, although some overlap of more general, disorder non-specific aspects seem to exist. Conclusion: Beyond stress-related transdiagnostic aspects, separate specific disturbances in certain neuronal circuits may lead to disorder-related symptoms inducing TD + ADHD in an additive way. Hence, within a classificatory categorical framework, the dimensional aspects of multilevel diagnostic-profiling seem to be a helpful precondition for personalized decisions on counselling and disorder-specific treatment in TD + ADHD.

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Altered urinary tetrahydroisoquinoline derivatives in patients with Tourette syndrome: reflection of dopaminergic hyperactivity?

Cited by 11 publications

References 18 publications

Neuroprotective Activity of Enantiomers of Salsolinol and N-Methyl-(R)-salsolinol: In Vitro and In Silico Studies

Neuroprotective Activity of Enantiomers of Salsolinol and N-Methyl-(R)-salsolinol: In Vitro and In Silico Studies

A Pilot Study on Plasma and Urine Neurotransmitter Levels in Children with Tic Disorders

Co-Occurrence of Tic Disorders and Attention-Deficit/Hyperactivity Disorder—Does It Reflect a Common Neurobiological Background?

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